docetaxel followed by cef (cyclophosphamide, epirubicin and 5-fluorouracil) compared to docetaxel and capecitabine followed by cex (cyclophosphamide, epirubicin and capecitabine) as adjuvant treatment for breast cancer

Conditions: Breast Cancer

Summary: this study compares two chemotherapy regimens as adjuvant treatment for breast cancer. the study participants are randomly allocated to receive either 3 cycles of docetaxel followed by 3 cycles of cef (cyclophosphamide, epirubicin and 5-fluorouracil) or to receive 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cex (cyclophosphamide, epirubicin and capecitabine). the study participants are required to to have a medium to high risk for breast cancer recurrence. the primary aim of the study is to investigate whether addition of capecitabine to a standard taxane/anthracycline regimen will influence recurrence-free survival.

this is an open-label, two-arm, randomized multi-center phase iii trial to compare efficacy and safety of a taxane-anthracycline regimen to a taxane-anthracycline-capecitabine regimen as adjuvant treatment of early breast cancer with an intermediate-to-high risk of cancer recurrence. patients diagnosed with early breast cancer with an estimated risk of 25% or greater for distant recurrence within 5 years from the diagnosis will be randomly allocated to one of the following 2 arms (1:1): * arm a -- 3 cycles of docetaxel 80 mg/m² intravenous (i.v.) (repeated on day \[d.\] 22); followed by 3 cycles of cef (cyclophosphamide 600 mg/m2 i.v., epirubicin 75mg/m² i.v., 5-fluorouracil 600 mg/m2 i.v., repeated on d. 22) * arm b -- 3 cycles of tx (docetaxel 60 mg/m² i.v., capecitabine twice daily 900 mg/m² given orally on days 1-15 of the cycle; cycle repeated on d. 22); followed by 3 cycles of cex (cyclophosphamide 600 mg/m2 i.v., epirubicin 75mg/m² i.v, capecitabine twice daily 900 mg/m² on days 1-15 of the cycle; cycle repeated on d. 22) locoregional radiotherapy is given according to the institutional practice after completing adjuvant chemotherapy (tx3/cefx3 or txx3/cexx3). all patients with er and/or pgr positive disease will receive adjuvant endocrine therapy. this will consist of 1 mg p.o. anastrozole (arimidexr) given for 60 months in women who were post-menopausal prior to chemotherapy (no menstrual periods for \> 6 months) or of tamoxifen 20 mg p.o. for 60 months in women who were pre-menopausal prior to chemotherapy. use of trastuzumab is allowed in her-2 positive disease. patients will be followed up for 5 years post-randomization.

Eligibility criteria:
inclusion criteria: to be eligible for inclusion in the study, each patient must fulfill each of the criteria below. * have provided written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice. * be female and 18 years of age or older. * have histologically confirmed invasive breast cancer. * high risk of breast cancer recurrence (\> 25% within the first 5 years without adjuvant therapy, \> 35% within the first 10 years) with one of the following: * regional node positive disease (pn+; tumor cells or tumor cell clusters \< 0.2 mm in diameter are not counted as metastases); * pathological n0 and pgr- and tumor size \> 20 mm. exclusion criteria: patients who fulfill any of the following criteria will be excluded: * \> 65 years of age. * "special type" histology (mucinous, papillary, medullary, or tubular breast cancer), when pn0. * er, pgr and her-2 status (via in situ hybridization or immunohistochemistry) not determined. * presence of distant metastases. * previous chemotherapy in the neoadjuvant setting. * non-ambulatory or who performance status \> 1. * pregnant or lactating women. women of childbearing potential (menstruating within 6 months of study entry or with no hysterectomy and age \< 55) with either a positive or no pregnancy test at baseline. * women of childbearing potential unless using a reliable and appropriate contraceptive method. (post-menopausal women must have been amenorrheic for at least 6 months to be considered of non-childbearing potential). * more than 12 weeks between breast surgery and date of randomization. * organ allografts with immunosuppressive therapy required. * major surgery (except breast surgery) within 4 weeks prior to study treatment start, or lack of complete recovery from the effects of major surgery. * participation in any investigational drug study within 4 weeks preceding treatment start. * patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake. * history of another malignancy within the last five years except cured basal cell carcinoma of skin or carcinoma in situ of the uterine cervix. * clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication) or myocardial infarction within the last 12 months. * abnormal laboratory values: * hemoglobin \< 10.0 g/dl, neutrophils \< 1.5 x 10\^9/l, platelet count \< 120 x 10\^9/l; * serum creatinine \> 1.5 x upper limit of normal (uln); * creatinine clearance (calculated per cockroft and gault) \< 50 ml/min; * serum bilirubin \> uln; * alat \> 1.5 x uln; * alkaline phosphatase \> 2.5 x uln. * serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease. * lack of physical integrity of the upper gastrointestinal tract or those who have clinically significant malabsorption syndrome. * inability to swallow tablets. * life expectancy of less than 3 months. * unwilling or unable to comply with the protocol for the duration of the study. * requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine.

Keywords: breast cancer chemotherapy adjuvant capecitabine docetaxel